PDF(Pubmed)
Abstract：
UNASSIGNED: Kidney transplantation (KT) is the best treatment for end-stage renal disease. Although long and short-term survival rates for the graft have improved significantly with the development of immunosuppressants, acute rejection (AR) remains a major risk factor attacking the graft and patients. The innate immune response plays an important role in rejection. Therefore, our objective is to determine the biomarkers of congenital immunity associated with AR after KT and provide support for future research.
UNASSIGNED: A differential expression genes (DEGs) analysis was performed based on the dataset GSE174020 from the NCBI gene Expression Synthesis Database (GEO) and then combined with the GSE5099 M1 macrophage-related gene identified in the Molecular Signatures Database. We then identified genes in DEGs associated with M1 macrophages defined as DEM1Gs and performed gene ontology (GO) and Kyoto Encyclopedia of Genomes (KEGG) enrichment analysis. Cibersort was used to analyze the immune cell infiltration during AR. At the same time, we used the protein-protein interaction (PPI) network and Cytoscape software to determine the key genes. Dataset, GSE14328 derived from pediatric patients, GSE138043 and GSE9493 derived from adult patients, were used to verify Hub genes. Additional verification was the rat KT model, which was used to perform HE staining, immunohistochemical staining, and Western Blot. Hub genes were searched in the HPA database to confirm their expression. Finally, we construct the interaction network of transcription factor (TF)-Hub genes and miRNA-Hub genes.
UNASSIGNED: Compared to the normal group, 366 genes were upregulated, and 423 genes were downregulated in the AR group. Then, 106 genes related to M1 macrophages were found among these genes. GO and KEGG enrichment analysis showed that these genes are mainly involved in cytokine binding, antigen binding, NK cell-mediated cytotoxicity, activation of immune receptors and immune response, and activation of the inflammatory NF-κB signaling pathway. Two Hub genes, namely CCR7 and CD48, were identified by PPI and Cytoscape analysis. They have been verified in external validation sets, originated from both pediatric patients and adult patients, and animal experiments. In the HPA database, CCR7 and CD48 are mainly expressed in T cells, B cells, macrophages, and tissues where these immune cells are distributed. In addition to immunoinfiltration, CD4+T, CD8+T, NK cells, NKT cells, and monocytes increased significantly in the AR group, which was highly consistent with the results of Hub gene screening. Finally, we predicted that 19 TFs and 32 miRNAs might interact with the Hub gene.
UNASSIGNED: Through a comprehensive bioinformatic analysis, our findings may provide predictive and therapeutic targets for AR after KT.
UNASSIGNED: A differential expression genes (DEGs) analysis was performed based on the dataset GSE174020 from the NCBI gene Expression Synthesis Database (GEO) and then combined with the GSE5099 M1 macrophage-related gene identified in the Molecular Signatures Database. We then identified genes in DEGs associated with M1 macrophages defined as DEM1Gs and performed gene ontology (GO) and Kyoto Encyclopedia of Genomes (KEGG) enrichment analysis. Cibersort was used to analyze the immune cell infiltration during AR. At the same time, we used the protein-protein interaction (PPI) network and Cytoscape software to determine the key genes. Dataset, GSE14328 derived from pediatric patients, GSE138043 and GSE9493 derived from adult patients, were used to verify Hub genes. Additional verification was the rat KT model, which was used to perform HE staining, immunohistochemical staining, and Western Blot. Hub genes were searched in the HPA database to confirm their expression. Finally, we construct the interaction network of transcription factor (TF)-Hub genes and miRNA-Hub genes.
UNASSIGNED: Compared to the normal group, 366 genes were upregulated, and 423 genes were downregulated in the AR group. Then, 106 genes related to M1 macrophages were found among these genes. GO and KEGG enrichment analysis showed that these genes are mainly involved in cytokine binding, antigen binding, NK cell-mediated cytotoxicity, activation of immune receptors and immune response, and activation of the inflammatory NF-κB signaling pathway. Two Hub genes, namely CCR7 and CD48, were identified by PPI and Cytoscape analysis. They have been verified in external validation sets, originated from both pediatric patients and adult patients, and animal experiments. In the HPA database, CCR7 and CD48 are mainly expressed in T cells, B cells, macrophages, and tissues where these immune cells are distributed. In addition to immunoinfiltration, CD4+T, CD8+T, NK cells, NKT cells, and monocytes increased significantly in the AR group, which was highly consistent with the results of Hub gene screening. Finally, we predicted that 19 TFs and 32 miRNAs might interact with the Hub gene.
UNASSIGNED: Through a comprehensive bioinformatic analysis, our findings may provide predictive and therapeutic targets for AR after KT.
摘要：
■肾移植（KT）是治疗终末期肾病的最佳方法。尽管随着免疫抑制剂的发展，移植物的长期和短期生存率显着提高，急性排斥反应（AR）仍然是攻击移植物和患者的主要危险因素。先天免疫应答在排斥反应中起重要作用。因此,我们的目标是确定KT后与AR相关的先天性免疫的生物标志物,并为未来的研究提供支持.
基于来自NCBI基因表达合成数据库(GEO)的数据集GSE174020进行差异表达基因(DEGs)分析,然后与分子特征数据库中鉴定的GSE5099M1巨噬细胞相关基因组合。然后，我们鉴定了DEGs中与M1巨噬细胞相关的基因，定义为DEM1Gs，并进行了基因本体论（GO）和京都基因组百科全书（KEGG）富集分析。使用Cibersort分析AR期间的免疫细胞浸润。同时,我们使用蛋白质-蛋白质相互作用（PPI）网络和Cytoscape软件来确定关键基因。数据集,来自儿科患者的GSE14328，GSE138043和GSE9493来源于成人患者，用于验证Hub基因。另外的验证是大鼠KT模型，用于进行HE染色，免疫组织化学染色，西方的Blot。在HPA数据库中搜索Hub基因以确认它们的表达。最后,我们构建了转录因子(TF)-Hub基因和miRNA-Hub基因的相互作用网络。
■与正常组相比，366个基因上调,AR组中有423个基因下调。然后，在这些基因中发现了106个与M1巨噬细胞相关的基因。GO和KEGG富集分析表明,这些基因主要参与细胞因子的结合,抗原结合，NK细胞介导的细胞毒性，激活免疫受体和免疫反应，和炎症NF-κB信号通路的激活。两个Hub基因,即CCR7和CD48，通过PPI和Cytoscape分析鉴定。它们已经在外部验证集中进行了验证，起源于儿科患者和成人患者，和动物实验。在HPA数据库中，CCR7和CD48主要在T细胞中表达,B细胞,巨噬细胞，以及这些免疫细胞分布的组织。除了免疫浸润,CD4+T,CD8+T，NK细胞,NKT细胞,AR组单核细胞显著增加，这与Hub基因筛选的结果高度一致。最后,我们预测19个TFs和32个miRNAs可能与Hub基因相互作用。
■通过全面的生物信息学分析，我们的研究结果可能为KT后AR提供预测和治疗靶点.
基于来自NCBI基因表达合成数据库(GEO)的数据集GSE174020进行差异表达基因(DEGs)分析,然后与分子特征数据库中鉴定的GSE5099M1巨噬细胞相关基因组合。然后，我们鉴定了DEGs中与M1巨噬细胞相关的基因，定义为DEM1Gs，并进行了基因本体论（GO）和京都基因组百科全书（KEGG）富集分析。使用Cibersort分析AR期间的免疫细胞浸润。同时,我们使用蛋白质-蛋白质相互作用（PPI）网络和Cytoscape软件来确定关键基因。数据集,来自儿科患者的GSE14328，GSE138043和GSE9493来源于成人患者，用于验证Hub基因。另外的验证是大鼠KT模型，用于进行HE染色，免疫组织化学染色，西方的Blot。在HPA数据库中搜索Hub基因以确认它们的表达。最后,我们构建了转录因子(TF)-Hub基因和miRNA-Hub基因的相互作用网络。
■与正常组相比，366个基因上调,AR组中有423个基因下调。然后，在这些基因中发现了106个与M1巨噬细胞相关的基因。GO和KEGG富集分析表明,这些基因主要参与细胞因子的结合,抗原结合，NK细胞介导的细胞毒性，激活免疫受体和免疫反应，和炎症NF-κB信号通路的激活。两个Hub基因,即CCR7和CD48，通过PPI和Cytoscape分析鉴定。它们已经在外部验证集中进行了验证，起源于儿科患者和成人患者，和动物实验。在HPA数据库中，CCR7和CD48主要在T细胞中表达,B细胞,巨噬细胞，以及这些免疫细胞分布的组织。除了免疫浸润,CD4+T,CD8+T，NK细胞,NKT细胞,AR组单核细胞显著增加，这与Hub基因筛选的结果高度一致。最后,我们预测19个TFs和32个miRNAs可能与Hub基因相互作用。
■通过全面的生物信息学分析，我们的研究结果可能为KT后AR提供预测和治疗靶点.
